Migraine headaches affect approximately 9% (21 million female; 7 million male) of the population in the United States. The worldwide estimate of incidence is 650 million. There are a number of different forms of migraine. A principal characteristic of all migraines is recurrence, and the pain can be moderate to severe if left untreated. For example, the headache may be unilateral, can be triggered by light, sound, smells, or other stimuli, and is often accompanied by nausea, vestibular symptoms, and visual distortions, or preceded by an aura.
Interventions for migraine are difficult, since the pain may involve multiple central nervous system structures and neurotransmitters. In many instances, the autonomic nervous system is involved, which leads to nausea, vomiting, and cardiovascular signs, as well as headache. Other substantial variations in migraine appear, ranging from ocular pain accompanied by vision loss or blindness, muscle tension, sinus pain, and vertebrobasilar pain associated with vertigo. A variation of migraine pain is generally called “trigeminal neuropathy,” and typically includes long-lasting oral pain, often arising from failed or compromised dental procedures, with trigeminal nerve (cranial nerve 5), facial nerve (cranial nerve 7), glossopharyngeal nerve (cranial nerve 9), or vagal (cranial nerve 10) irritation involved. The disorder can be accompanied by severe pain for many years, paraesthesias (such as tickling, odd sensations, or numbness), or sensations of burning. The so-called “burning mouth” syndrome, characterized by long-lasting, severe pain in the tongue or oral cavity i.e., stomatodynia and glossodynia, as well as severe, overwhelming pain from mild stimulation to the face, trigeminal neuralgia, also appears. These variations emphasize the complexity of migraine and associated pain syndromes.
Classical approaches to pain intervention include pharmacologic intervention, electrical stimulation, including transcranial electrical stimulation (DaSilva et al., 2012, The Journal of Head and Face Pain, 52: 1283-1295), electrical stimulation of the forehead, deep brain structures, or nerves within the brain or deep to the surface (Meng et al., 2013, Neurology, 81: 1102-1103; Mosqueira et al., 2013, Rev Neurol, 57(2): 57-63; Schoenen et al., 2013, Neurology, 0(8): 697-704), and Botox application (Silberstein et al., 2000; The Journal of Head and Face Pain, 40: 445-450) to reduce innervation to scalp muscles. Electrical stimulation of the peripheral skin poses a risk of injury to the underlying tissue, and can be uncomfortable. Outcomes of muscle paralysis procedures from Botox are often transient, and require skilled professional intervention, with careful attention to infection risk. The stimulation procedures requiring deep brain stimulation or access to nerves involve major surgery with substantial anesthetic and infection concerns (Pedersen et al., 2013; Cephalagia, 33(14): 1179-1193). Other procedures can vary in effectiveness. A range of pharmaceutical interventions exist (Olesen and Ashina, 2011, Trends in Pharmacological Sciences, 33(6): 352-359), and include serotonin agonists and nitric oxide antagonists. Many of these pharmaceutical interventions have severe side effects, including excessive sleepiness and addiction, especially to opioid agents. The impaired cognitive, arousal, gastric irritation, vestibular, and affective consequences of pharmaceutical agents pose concerns. Trigeminal neuralgia typically requires seizure medication, vascular decompression surgery, or lesioning of areas of the 5th cranial nerve (Janetta, 1980, Ann Surg, 192(4): 518-525). The invasiveness and severity of side effects make none of these options optimal.
Since migraine headaches involve multiple central nervous system (CNS) modulators, these classical approaches to pain intervention are not sufficiently targeted. There is thus a need for a migraine pain intervention via stimulation of multiple cranial nerves in a pattern that interferes with pain perception. Ideally, these stimuli would be non-invasive, and be patient-controllable, with the patient adjusting the stimuli when pain appears. The patient should also have the option to “condition” CNS processes to suppress migraine development, i.e. apply stimulation to “train” the brain to suppress brain activity that might lead to later migraine onset. Accordingly, there is a need in the art for alternative, non-invasive, devices and procedures that are easy to use for reducing headache pain and alleviating symptoms associated with migraine pain. The present invention satisfies this need.